Molecular-level insights into the therapeutic potential of lidocaine: effects on proliferation, autophagy, and cellular impedance in human oral cells

BACKGROUND: Local anesthesia is widely used in dental treatments such as extractions, implants, gum grafts, and jaw surgery. Recent studies have examined the effects of anesthetics, particularly lidocaine, on postoperative outcomes in patients with cancer; however, its specific role in cancer progression in the perioperative context remains to be explored. METHODS: In this study, we aimed to explore the effects of lidocaine on oral epidermoid carcinoma meng-1 (OECM-1) and gingival epithelial Smulow-Glickman (SG) cells using cell viability, flow cytometry, real-time polymerase chain reaction, western blotting, Electric Cell-Substrate Impedance Sensing, and RNA-sequencing analyses. RESULTS: Our findings revealed contrasting effects of lidocaine on these cell types. In OECM-1 cells, lidocaine suppressed metabolic activity (> 4 mM), cellular proliferation, S-phase population, and late apoptosis (< 4 mM). It also altered mitochondrial membrane potential, induced hypoxia and autophagy, and affected the expression of specific proteins and mRNAs. In contrast, SG cells exhibited different responses, with lidocaine influencing cell cycle profiles; increasing the number of apoptotic cells, cytosolic reactive oxygen species (ROS), and JC-1 aggregates; and altering mRNA expression. Additionally, the combination index analysis showed that lidocaine worked synergistically with cisplatin and 5-fluorouracil in both OECM-1 and SG cells. The cellular impedance patterns indicated similarities between the effects of lidocaine and those of lidocaine and cisplatin combination therapy. CONCLUSION: In this study, we identified significant differences between OECM-1 and SG cells in terms of the effects of lidocaine on cell cycle profiles, cytosolic ROS, and mitochondrial potential. These results suggest that local anesthetics, such as lidocaine, may play crucial roles in combination therapies for oral cancers and in wound healing in post-gum grafts beyond their conventional use in pain management.